Distinct roles of IL-18 and IL-1ß in murine model of macrophage activation syndrome.
J Allergy Clin Immunol
; 152(4): 940-948.e6, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-37352976
ABSTRACT
BACKGROUND:
IL-18 and IL-1ß play a central role in the pathogenesis of systemic juvenile idiopathic arthritis and its life-threatening complication, macrophage activation syndrome (MAS).OBJECTIVES:
This study aimed to clarify the role of IL-18 and IL-1ß in the pathogenesis of MAS.METHODS:
We developed a mouse model to evaluate the role of each cytokine with Toll-like receptor 9 stimulation after continuous infusion with IL-18, IL-1ß, and a combination of both for 7 days. The symptoms and laboratory findings were compared among the IL-18, IL-1ß, and combination (IL-18+IL-1ß) groups.RESULTS:
Body weight was significantly decreased in the IL-1ß and combination groups. Splenomegaly was observed in all groups, whereas hepatomegaly was noted in the IL-18 group only. Decreased T-cell numbers, anemia, and thrombocytopenia were observed in the combination group. IFN-γ, CXCL9, and IL-12A mRNA levels were upregulated and IL-10 mRNA levels in the spleen were downregulated in the IL-18 group. Hepatomegaly and splenomegaly in the IL-18 group were observed in a dose-dependent manner. TNF-α, CXCL9, and IL-12A mRNA levels were upregulated only in those mice with extremely elevated plasma IL-18 levels.CONCLUSION:
IL-18 and IL-1ß have distinct roles in the pathogenesis of MAS. Dual blockade of IL-18 and IL-1ß might be necessary to treat MAS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão